HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster.
Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been de...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3561118?pdf=render |
| _version_ | 1818456961258094592 |
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| author | Yan Li Divya Padmanabha Luciana B Gentile Catherine I Dumur Robert B Beckstead Keith D Baker |
| author_facet | Yan Li Divya Padmanabha Luciana B Gentile Catherine I Dumur Robert B Beckstead Keith D Baker |
| author_sort | Yan Li |
| collection | DOAJ |
| description | Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIFa and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIFa in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs. |
| first_indexed | 2024-12-14T22:34:59Z |
| format | Article |
| id | doaj.art-80e0f829b75d499ea6d646c4949e4599 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T22:34:59Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-80e0f829b75d499ea6d646c4949e45992022-12-21T22:45:10ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0191e100323010.1371/journal.pgen.1003230HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster.Yan LiDivya PadmanabhaLuciana B GentileCatherine I DumurRobert B BecksteadKeith D BakerLow-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIFa and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIFa in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs.http://europepmc.org/articles/PMC3561118?pdf=render |
| spellingShingle | Yan Li Divya Padmanabha Luciana B Gentile Catherine I Dumur Robert B Beckstead Keith D Baker HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. PLoS Genetics |
| title | HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. |
| title_full | HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. |
| title_fullStr | HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. |
| title_full_unstemmed | HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. |
| title_short | HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. |
| title_sort | hif and non hif regulated hypoxic responses require the estrogen related receptor in drosophila melanogaster |
| url | http://europepmc.org/articles/PMC3561118?pdf=render |
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